Objective: To investigate the influence of sorafenib on growth and expressions of tumor-related genes in human hepatocellular carcinoma (HCC) cells in vitro. Methods: Human HCC cells (Hep3B2.1-7) were exposed to different concentrations (0, 5, 10, and 20 μmol/L) of sorafenib for 24 h, and then, the cell proliferation was analyzed by CCK-8 assay, and the mRNA and protein expressions of p53, PTEN and TGF-β1 in the HCC cells were determined by real-time PCR and Western blot, respectively. Results: Compared with the group of cells with 0 μmol/L sorafenib treatment (control group), in the other groups of cells with sorafenib treatment, the cell proliferation rates were all significantly decreased (all P<0.05); the mRNA and protein expressions of p53 and PTEN were significantly increased, while the mRNA and protein expressions of TGF-β1 were significantly decreased (all P<0.05). All these effects of sorafenib showed a certain concentration-dependent manner. Conclusion: Sorafenib can inhibit the growth of human HCC cells in vitro, and the mechanism may be attributed to its regulating the expressions of tumor-related genes.